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Biomedical subjects

M L Hess

Publications and source records attributed to M L Hess.

At least 91 records · Page 5Linked to original sources
PubMed1985

Serial coronary angioplasty for atherosclerosis following heart transplantation.

A 51-year-old man underwent orthotopic heart transplantation for end-stage ischemic cardiomyopathy. Forty-six months after the operation significant coronary artery disease was demonstrated in the allografted heart, with severe (90% to 95%) proximal stenosis of the left anterior descending artery as well as diffuse distal and smaller branch lesions. Percutaneous transluminal coronary angioplasty of the proximal left anterior descending artery lesion was successfully performed, reducing the stenosis to a 20% to 30% narrowing. Sixteen months later, repeated angiography showed sustained improvement of the proximal left anterior descending artery lesion and development of new significant lesions in the mid-left anterior descending and left circumflex coronary arteries. Coronary angioplasty of the mid-left anterior descending and proximal circumflex artery lesions was successfully performed and an angiogram four months later showed continued angiographic improvement at each of the distal sites. This case represents the first reported coronary artery angioplasty in a heart transplant recipient. It demonstrates the successful application of a non-operative myocardial revascularization procedure using percutaneous transluminal coronary angioplasty to achieve sustained palliation of significant coronary artery disease following heart transplantation.

Angioplasty, Balloon↗
PubMed1985

Identification of hydrogen peroxide and hydroxyl radicals as mediators of leukocyte-induced myocardial dysfunction. Limitation of infarct size with neutrophil inhibition and depletion.

Neutrophil infiltration of the myocardium is an important component of such diverse disease entities as myocarditis, ischemia, and ischemia-reperfusion injury. We have hypothesized that activated neutrophils are capable of disrupting myocardial function via an oxygen free-radical mechanism. Human neutrophils activated with phorbol myristate acetate disrupted calcium transport by canine cardiac sarcoplasmic reticulum, and this process was inhibited by a combination of superoxide dismutase and catalase. In addition, the activated neutrophil system was also inhibited by the combination of cyclooxygenase inhibitors (ibuprofen and indomethacin) and catalase and accelerated by MK-447. These results incriminate both hydrogen peroxide and the hydroxyl radical as mediators of neutrophil-induced myocardial dysfunction. A test of this hypothesis in vivo was performed by neutrophil-depleting dogs with anti-canine leukocyte antisera prior to coronary artery ligation. Following 6 hr of reperfusion, there was a 43% reduction in infarct size compared to non-immune-sera-injected animals. We conclude that oxygen free radicals generated by neutrophils are capable of inducing significant myocardial injury and play an important role in the pathophysiology of ischemia reperfusion injury.

Adenosine Triphosphatases↗
PubMed1985

Prevention of free radical-induced myocardial reperfusion injury with allopurinol.

Growing evidence supports the concept that oxygen free radicals are an important cause of myocardial ischemic and reperfusion injury. This study was designed to determine if toxic oxygen metabolites may exacerbate ischemic injury upon reoxygenation. Left ventricular function was studied in a group of seven dogs receiving intermittent, 4 degrees C, hyperosmolar, hyperkalemic (KCI 25 mEq/L) saline cardioplegic solution. This group was compared to a group (n = 7) receiving a hyperkalemic (KCI 25 mEq/L) cardioplegic solution designed to scavenge superoxide anion and hydroxyl radical: superoxide dismutase (3,000 U/ml) and mannitol (325 mOsm/L). A third group of five animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours and hyperkalemic saline cardioplegic solution. After 60 minutes of ischemia (10 degrees to 15 degrees C) and 45 minutes of reperfusion, left ventricular mechanical function was better in the groups receiving free radical scavengers and allopurinol pretreatment than in the group receiving only hyperkalemic saline cardioplegic solution. Free radical scavengers preserved myocardial function in this model of hypothermic global ischemia and reperfusion. Our data support the concept that injury occurs primarily during reperfusion with the generation of oxygen free radicals via the hypoxanthine-xanthine oxidase reaction. Allopurinol has potential clinical application in the prevention of reperfusion injury.

Allopurinol↗
PubMed1984

Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury.

We strongly support the original intriguing hypothesis of Hearse et al. that the oxygen paradox and the calcium paradox are facets of the same problem. We would propose that the major similarity is a final common pathway leading to intracellular calcium overload and the sequelae of the resultant increase in intracellular calcium. In addition, we would propose that the oxygen paradox and ischemic/reperfusion injury are also facets of the same problem with the major similarity being the reintroduction of molecular oxygen to a previously hypoxic myocardium. Finally, we would suggest that the common pathway leading to intracellular calcium overload in the oxygen paradox and ischemic/reperfusion injury and to a lesser extent the calcium paradox involves the generation of oxygen free radicals. The source of oxygen free radical generation in the calcium paradox is perhaps less obvious than in the oxygen paradox. It is proposed that during calcium-free perfusion, calcium is leached from the plasmalemma of the myocyte. There is a resulting increase in membrane fluidity. Within the plasmalemma are a number of calcium sensitive phospholipases. Upon reperfusion with a calcium replete medium, calcium could pool around these membrane bound phospholipases initiating a chain reaction of lipid peroxidation which actually is perpetuated by free radical generation (Equations 5A-5C). Lipid peroxidation opens channels within the plasmalemma rendering a 'leaky' sarcolemma. It is through these channels that calcium could flow down its concentration gradient into the cell. The increased calcium accumulation at the mitochondria would lead to an uncoupling of oxidative phosphorylation. With depleted energy stores, the mitochondria and sarcoplasmic reticulum no longer serve as calcium sinks. This would contribute to the calcium overload seen upon reperfusion. The role of oxygen free radical production would appear to occur during the hypoxic phase of the oxygen paradox and the ischemic phase of ischemic/reperfusion injury and during the reoxygenation/reperfusion phases. With the onset of hypoxia and/or myocardial ischemia there is an increase in reducing equivalents, disturbance and dissociation of intramitochondrial electron transport and release of ubisemiquinone, flavoproteins and superoxide radicals. The increase in reducing equivalents includes NADPH and, in ischemia, catecholamines, hypoxanthine and an increase on xanthine oxidase activity. All of these substrates are capable of participating in free radical production. This increase in free radical production in ischemic tissue is enhanced by acidosis which in the ischemic and hypoxic myocardium approaches pH 6.0-6.4.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Neutrophil-derived, oxygen free radical-mediated cardiovascular dysfunction.

Oxygen free radicals and their metabolites generated from activated neutrophils have been implicated in mediating the cardiovascular dysfunction of such diverse etiologies as myocardial ischemia and reperfusion injury, Gram negative sepsis, myocarditis and acute cardiac allograft rejection, but a direct demonstration of neutrophil derived oxygen free radical mediation of cardiovascular dysfunction has not been accomplished. In this study, we have demonstrated that activation of the canine neutrophil system, in vivo, results in the generation of oxygen free radicals that are capable of disrupting cardiovascular function producing a significant decrease in mean arterial pressure and cardiac index without any significant effect on the conduction system of the myocardium. Neutrophil depletion or pretreatment with superoxide dismutase and catalase inhibited the effects of activated neutrophils. This study provides evidence that neutrophil-derived reduced oxygen intermediates are able to induce severe cardiovascular dysfunction.

Animals↗
PubMed1984

Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates.

Generation of oxygen free radicals by xanthine acting on xanthine oxidase as a substrate significantly depressed calcium transport by sarcoplasmic reticulum in canine whole heart homogenates at 37 degrees C. At pH 7.0, this effect was completely inhibited by the addition of superoxide dismutase (SOD), a scavenger of the superoxide anion radical. At pH 6.4, SOD (5 to 20 micrograms X ml-1) was ineffective but catalase (20 micrograms X ml-1) was able to inhibit the effects of the xanthine-xanthine oxidase system. SOD + catalase (20 micrograms X ml-1) and SOD + mannitol, a scavenger of the hydroxyl free radical, inhibited the effects of the xanthine-xanthine oxidase system at pH 6.4. Preincubation at pH 6.4, in the absence of an exogenous free radical generating system, depressed calcium transport. This depression was more severe the longer the duration of incubation. However, return of the pH to 7.0 after preincubation at pH 6.4 partially restored calcium uptake velocity. The degree of reversibility was decreased the longer the period of incubation at pH 6.4. SOD reversed the effects of incubation at pH 6.4 for 5 min, but not those for incubations of 10 and 15 min. Mannitol alone was ineffective. The combinations of SOD and mannitol significantly reversed the effects of pH 6.4 up to 15 min. These results demonstrate that both exogenously generated and endogenously generated free oxygen radicals are capable of depressing calcium transport by cardiac sarcoplasmic reticulum in the whole heart homogenate in the presence of endogenous scavenging systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1984

Characterization of cardiac sarcoplasmic reticulum dysfunction during short-term, normothermic, global ischemia.

It has been proposed that breakdown of the excitation-contraction coupling system plays a pivotal role in myocardial dysfunction during the course of acute ischemia. We tested this hypothesis by characterizing the function of the sarcoplasmic reticulum at pH 7.1 and 6.4 after 7.5, 15, and 30 minutes of canine normothermic global ischemia. At pH 7.1, whole heart homogenate sarcoplasmic reticulum demonstrated a 49% depression of oxalate-supported calcium uptake at 7.5 minutes of ischemia, which progressed to 85% at 30 minutes of ischemia. At pH 6.4, control homogenate calcium uptake rates were significantly depressed, accompanied by a further depression in the ischemic groups. Isolated sarcoplasmic reticulum calcium uptake mirrored the effects of the whole heart homogenate. Calcium-stimulated magnesium-dependent ATPase (calcium-ATPase) activity was significantly depressed by both ischemia and acidosis, with a decrease in the coupling ratio (mumol calcium/mumol ATP) at 15 and 30 minutes of ischemia. Acidosis (pH 6.4) significantly shifted the sarcoplasmic reticulum pCalcium-ATPase curve to the right, increasing 50% activation from pCalcium 6.0 to 5.5 and depressing the maximum velocity (pH 7.1 = 2.06 +/- 0.14; pH 6.4 = 1.41 +/- 0.05 mumol Pi/mg per min; P less than 0.01). With ischemia, there was a progressive decrease in maximal activation of the calcium-ATPase enzyme and a progressive shift in calcium sensitivity to a higher concentration. Steady state calcium uptake, in the absence of oxalate, demonstrated a similar depression after 7.5 and 15 minutes of ischemia at pH 7.1 and 6.4, associated with a significant increase in the passive permeability coefficient for calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1984

Effect of examination time of day on the quality of real-time cholesonograms.

Real-time sector scans of the gallbladder and common hepatic duct were performed at 7:00 a.m., 1:00 p.m., and 5:00 p.m. on 16 volunteers eating a regular diet. Technically satisfactory but not ideal scans of the common duct could be obtained irrespective of dietary status or time of day. As the day progressed, about one-half of subjects having gallbladder scans showed a significant decrease in bile volume, spurious gallbladder wall thickening, or compromised images from excessive intestinal gas. The data suggest that, if possible, gallbladder imaging should be performed early in the morning after overnight fasting, even when high-resolution sector scanners are used. However, because nearly one-half of patients can have satisfactory scans under any circumstances, cholesonograms should be performed in emergency situations or in those instances where patients would suffer inconvenience or financial hardship by delay of the study for an additional day.

Adult↗
PubMed1984

Role of angiotensin I and glucagon in canine endotoxin shock: effect of converting enzyme inhibitor and prior immunization.

he intermediate and latter stages of canine endotoxin shock are characterized by a progressive decrease in cardiac output, increase in total peripheral resistance, and hypoglycemia. We have hypothesized that the renin-angiotensin system and glucagon may mediate the loss of cardiovascular and glucose homeostasis. E. Coli endotoxin shock (1 mg/kg; 055:B5) was induced in three groups of dogs and systemic hemodynamics, angiotensin I activity, and glucagon were monitored for 5 hr; endotoxin shock (n = 13); endotoxin shock + prior immunization with J5 mutant of E coli 0111 (n = 5); Endotoxin + captopril (20 micrograms/kg/hr; n = 9); and sham-operated time-matched controls (n = 8). Thirty minutes postshock, angiotensin I and glucagon began to increase. Angiotensin I activity reached a peak at 60 min postendotoxin (90 +/- 25 vs 5 +/- ng/ml/hr; p less than 0.001) and plateaued. Increased glucagon levels plateaued at 3.5 hr postshock (1500 +/- 200 vs 155 +/- 77 pg/ml; p less than 0.001). Cardiac output began to progressively decrease, total peripheral resistance began to increase, and persistent hypoglycemia developed at 3 hr postshock. Captopril inhibited the increase in total peripheral resistance and had no effect on the decrease in cardiac output or the hypoglycemia. The initial glucagon response was attenuated but there was no difference at 5 hr (950 +/- 150 vs 1200 +/- 200 pg/ml). Prior immunization significantly preserved cardiac output, total peripheral resistance, plasma glucose levels, glucagon levels, and angiotensin I activity. It is concluded that 1) the renin-angiotensin system is a physiologic and not a pathophysiologic compensatory mechanism during the course of endotoxin shock and that inhibition of this system is deleterious; 2) glucagon may serve as an important mediator of both the myocardial dysfunction and glucose dyshomeostasis of endotoxin shock; and 3) immunological inhibition of the initial phase of endotoxin shock significantly preserves cardiovascular and glucose homeostasis and adds support to the concept that the initial vascular phase of endotoxin shock plays a primary role in determining the severity of the endotoxin/septic shock syndrome.

Angiotensin I↗
PubMed1983

Oxygen radicals and vascular damage.

The effects of topical application of agents which produce oxygen radicals on cerebral arterioles were studied in anesthetized cats. Xanthine oxidase plus xanthine, which produced superoxide anion radical, hydrogen peroxide, and hydrogen peroxide plus ferrous sulfate, which produced the free hydroxyl radical, induced sustained dilation, reduced responsiveness to the vasoconstrictor effect of hypocapnia, and destructive lesions of the endothelium and of the vascular smooth muscle. Similar effects were produced by arachidonate, 15-HPETE, and PGG2. The effect of arachidonate was inhibited by mannitol, a free hydroxyl radical scavenger, the effect of PGG2 was inhibited by SOD, the effect of 15-HPETE was inhibited by either catalase or SOD. These results suggest that these cerebral vascular abnormalities were produced by a single destructive free radical, probably the hydroxyl free radical, generated via interaction of superoxide and hydrogen peroxide. Cerebral vascular abnormalities similar to those produced by oxygen radicals were also seen after experimental concussive brain injury or after acute hypertension. After brain injury, activation of phospholipase C and increased brain prostaglandin concentration were demonstrated. The vascular effects of brain injury and acute hypertension were inhibited by free radical scavengers. The results suggest that, in these conditions, vascular damage is induced by oxygen radicals generated from arachidonate in association with increased prostaglandin synthesis.

Animals↗
PubMed1983

Mediation of sarcoplasmic reticulum disruption in the ischemic myocardium: proposed mechanism by the interaction of hydrogen ions and oxygen free radicals.

Acute myocardial ischemia results in a decrease in developed tension and an increase in resting tension. A breakdown of the excitation-contraction coupling system can explain the behavior of the ischemic muscle at a subcellular level. We have identified a specific defect in the sarcoplasmic reticulum (SR) from the ischemic myocardium; i.e., the uncoupling of calcium transport from ATP hydrolysis. The mediators of this excitation-contraction uncoupling process have not been identified. It is now established that the intracellular pH of the ischemic myocardium is in the range of 6.4 but the role of protons and potential role of free radicals have not been identified. We have hypothesized that protons and free radicals may interact to produce the excitation-contraction uncoupling of the ischemic myocardium. Cardiac SR was isolated from the wall of canine left ventricle and calcium uptake velocity and Ca2+ stimulated-Mg2+ dependent ATPase activity determined. Increasing proton concentration between pH 7.0 and 6.4 significantly reduced calcium uptake rates (pH 7.0 = 0.95 +/- 0.02; 6.4 = 0.50 +/- 0.02 mumoles Ca2+/mg-min; p less than 0.01) with no effect on ATPase activity. Calculated coupling ratios (mumoles Ca2+/mumoles Pi) decreased from 0.87 +/- 0.06 at pH 7.0 to 0.51 +/- 0.05 at pH 6.4. At pH 7.0, the generation of exogenous free radicals from the xanthine-xanthine oxidase system significantly depressed both calcium uptake rates (Control = 0.95 +/- 0.02; X+XO = 0.15 +/- 0.02) and ATPase activity (Control = 1.05 +/- 0.02; X+XO + 0.30 +/- 0.01 mumoles Pi/mg-min; p less than 0.01). The decreases in calcium uptake and in ATPase activity were completely reversible with superoxide dismutase (SOD). At pH 6.4 in the presence of xanthine and xanthine oxidase, there is a further depression of calcium uptake rates (Control = 0.50 +/- 0.02; X+XO = 0.11 +/- 0.01; p less than 0.05) but there is no SOD reversible component. The addition of SOD + 20mM mannitol normalized calcium transport at pH 6.4. The calculated coupling ratio at pH 6.4 in the presence of free radicals was 0.13. In contrast sarcoplasmic reticulum isolated from ischemic myocardium demonstrated a significant depression of calcium uptake rates at pH 7.1 which was further accentuated at pH 6.4. Ca2+-ATPase was significantly depressed at pH 7.1 but there was no accentuation at pH 6.4. It is concluded that no single species of free radical can explain the intracellular excitation-contraction uncoupling of the ischemic myocardium. The system can be explained by the interaction of hydrogen ions and superoxide anions producing both injury to the sarcoplasmic reticulum and the formation of lipid free radicals with hydroxyl-like activity.

Adenosine Triphosphatases↗
PubMed1983

Characterization of free radical-mediated damage of canine cardiac sarcoplasmic reticulum.

In vitro generation of free radicals by xanthine oxidase acting on xanthine as substrate depressed steady-state calcium uptake by canine cardiac sarcoplasmic reticulum vesicles. The effect of free radicals on the calcium-dependent ATPase activity of the SR vesicles was pH dependent. At pH 7.0, ATPase activity was decreased, but at pH 6.4 it was unchanged. Exposure to free radicals increased the passive permeability of the vesicles to calcium. This increase was inhibited by superoxide dismutase (SOD) at pH 7.0, and SOD plus mannitol at pH 6.4. The increased permeability per se was insufficient to explain the effects of free radicals on ATPase activity, since the calcium ionophore A23187 was unable to mimick these effects. Direct measurement of the number and turnover of the pump units indicated that the number of units was unchanged but turnover was decreased by free radicals at pH 7.0. The overall data suggest at least two mechanisms of free radical damage, one associated with an increase in passive permeability and another associated with an as yet undefined change in some specific steps of the ATPase reaction.

Animals↗
PubMed1983

Fibrinolytic effects of intracoronary streptokinase administration in patients with acute myocardial infarction and coronary insufficiency.

Serial coagulation studies were obtained in 25 patients treated with intracoronary streptokinase infusion for myocardial infarction (23 patients) or coronary insufficiency (two patients) to determine the frequency of systemic fibrinolytic activity. Clotting studies were obtained before and after infusion and at 4-hour intervals until normalization. Intracoronary thrombolysis was successful in 20 of 23 patients (87%) with myocardial infarction. Streptokinase dosage in this study was 201,000 +/- 74,000 IU (+/- SD). Systemic fibrinolytic activity, defined as greater than 70% reduction of fibrinogen using a functional assay (Claus method), occurred in 22 of 25 patients (88%) and was present at a mean streptokinase dosage of 119,000 +/- 52,000 IU. Fibrinogen in the total population decreased from 342 +/- 80 to 87 +/- 94 mg% (p less than 0.0001). In patients with systemic effect, the mean fibrinogen level after infusion was 17% of baseline, increased to 43% at 24 hours, and returned to normal at 30 hours. Plasminogen decreased to 7% of baseline activity after infusion (p less than 0.0001), was 44% of baseline at 24 hours, and returned to normal at 48 hours. Intraprocedural sampling during infusion showed reduction of fibrinogen by 25% after 30,000 IU (p less than 0.0005) and by 71% at 120,000 IU (p less than 0.0001); plasminogen decreased by 50% after 30,000 IU (p less than 0.0001) and by 84% at 120,000 IU (p less than 0.0001). Prothrombin time increased from 11.5 +/- 0.8 seconds to 22.0 +/- 7.8 seconds after infusion (p less than 0.0001) and returned to normal at a mean of 18 +/- 11 hours after infusion. Partial thromboplastin time was markedly prolonged (greater than 100 seconds) after infusion, returned to less than or equal to 2 times control at 5 +/- 2 hours, and returned to normal at 9 +/- 4 hours after infusion. Fibrinogen degradation products were less than 10 micrograms/ml before infusion, increased to greater than 40 micrograms/ml after infusion, and remained greater than 40 micrograms/ml in 40% of patients at 24 hours after infusion. These data indicate that systemic fibrinolytic activity occurs in a high percentage of patients with "low-dose" intracoronary streptokinase infusion and that coagulation variables may be altered for 24-48 hours after infusion.

Adult↗
PubMed1983

Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum. Participation of the cyclooxygenase pathway.

Human peripheral blood leukocytes, activated by phorbol myristate acetate, disrupt canine sarcoplasmic reticulum calcium transport, in vitro, by an oxygen-derived free radical mechanism. Activated leukocytes significantly depress Ca++ uptake activity and Ca++ -stimulated, Mg++ -dependent ATPase activity. The depression is completely inhibited by sodium-azide (0.1 mM) or the combination of superoxide dismutase (10 micrograms/ml) and catalase (10 micrograms/ml). Exogenous hydrogen peroxide (0.441-4.41 mM) uncoupled Ca++ uptake activity from ATP hydrolysis, and this effect was inhibited by catalase. Mannitol alone did not inhibit the effects of activated leukocytes, but superoxide plus mannitol (20-100 mM) resulted in normal ATPase activity, while Ca++ uptake remained depressed. In the presence of indomethacin and ibuprofen, activated leukocytes depressed Ca++ uptake and had no effect on ATPase activity. 2-Amino-methyl-4-t-butyl-6-iodophenol (MK-447) further depressed Ca++ uptake and partially inhibited the effect on ATPase activity. Indomethacin plus catalase completely inhibited the effects of activated leukocytes on cardiac sarcoplasmic reticulum. We conclude, first, that activated leukocytes depress canine cardiac sarcoplasmic reticulum Ca++ transport by an oxygen-free radical mechanism with the generation of hydrogen peroxide and hydroxyl radical. In addition to the classical membrane NADPH oxidase system, significant oxygen radical generation can occur through the cyclooxygenase pathway of arachidonic acid metabolism, and seems to be responsible for the generation of the hydroxyl radical.

Adenosine Triphosphatases↗